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Low-Dose Ketamine for Pain Management in the Emergency Department: Can it tame the pain?

Merissa De La Garza, PharmD PGY1 Pharmacy Resident

Baptist Health System Pharmacotherapy Division, University of Texas at Austin College of Pharmacy

Pharmacotherapy Education and Research Center, UT Health San Antonio May 10, 2019

Learning Objectives

1. Discuss current available pharmacotherapy approaches and limitations for acute pain2. Identify the pharmacologic properties of ketamine3. Develop an evidence-based recommendation for low-dose ketamine (LDK) as an

analgesic agent in the emergency department (ED)

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Pain in the Emergency Department

I. Background and epidemiology1-2

a. Pain is the most common presenting complaint to the EDb. Up to 78% of patients present to the ED with acute painc. From 1996 to 2015, ED visits have risen over 46% from 90.3 million to 136 milliond. Roughly 45% of ED visits involve either moderate or severe pain

II. Studies showing a lack of satisfactory pain management3-4

a. Todd KH et al.i. Of patients presenting to ED with pain complaint, 2/3 of patients never had

assessment of pain documentedii. 1/3 of patients never had a pain reassessment

iii. Upon discharge, 43% of patients were still in moderate to severe painb. Wilson JE et al.

i. 33% of patients received suboptimal analgesiaii. 69% of patients waited more than 1 hour to receive analgesics

iii. 42% of patients waited more than 2 hours to receive analgesics

III. Barriers to Effective Pain Management5-8

a. Provider Barriersi. Lack of basic knowledge and formal education on pain management

ii. Concerns about addictionb. Patient Barriers

i. Underreporting painii. Fears of addiction

c. Emergency Department Barriersi. Fast paced environment

ii. Lack of established patient-provider relationship

Pain

I. Definition of pain9

a. Unpleasant sensory and emotional experience associated with actual or potentialtissue damage

II. Pathophysiology of Pain10

a. Pain receptors (nociceptors) in the skin are activated by tissue damageb. Signals travel up the peripheral nerves to the spinal cordc. Within the spinal cord, neurotransmitters are released that activate other nerves

that pass signals to the braind. Thalamus in the brain relays signals to the somatosensory cortex (responsible for

sensation), to the frontal cortex (responsible for thinking) and the limbic system(emotional response)

e. End result is sensation of pain and an emotional reaction such as feeling irritated orannoyed

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III. Types of Pain11

a. Anatomical locationi. Somatic

1. Peripheral tissue injury2. Sharp, stabbing or dull pain; can be localized

ii. Visceral1. Organ injury2. Vague characteristics (i.e. cramping); difficult to localize

b. Underlying etiologyi. Nociceptive

1. Result of direct tissue injury from a noxious stimulusii. Neuropathic

1. Result of direct injury to nerves leading to an alteration in sensorytransmission

2. Caused by central nervous system (CNS) and peripheral nervoussystem (PNS) disorders

iii. Inflammatory1. Pain caused by inflammation2. Result of released inflammatory mediators that control nociceptive

inputiv. Psychogenic

1. Somatic manifestation of psychiatric illness or exacerbation of painseverity due to previous experience, poor coping mechanisms, orsocial history

c. Temporal naturei. Acute

1. Pain related to acute injury, harm, or repair and often shorterduration (typically less than 30 days)

2. Examples: bone fractures, appendicitisii. Chronic/persistent

1. Pain that lasts longer than the expected time of healing2. Examples: diabetic neuropathy, low back pain

iii. Acute-on-chronic1. Acute exacerbation of a chronic pain syndrome2. Examples: sickle cell pain episodes

d. Pain Intensityi. Mild

ii. Moderateiii. Severe

e. Screening and assessment tooli. Numeric Rating Scale (NRS) (Figure 1)

1. Most commonly used pain scale2. Patient reported pain on a scale from 0-10

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Figure 1. NRS Rating Scale

Consensus Guidelines12

I. American Academy of Emergency Medicine (AAEM) White Paper on Acute PainManagement in the ED

a. Goalsi. Treatments should be: Patient-specific, pain syndrome-targeted, and based

on appropriate non-pharmacological and pharmacological approachesii. ED clinicians are in a unique position to provide optimal analgesia, educate

patients and combat the opioid epidemicII. Treatments

a. Non-pharmacologic approachesi. Heat or cold therapies

ii. Consider osteopathic manipulation techniques for patients presenting withpain syndromes of skeletal, arthrodial and myofascial origins

b. Multimodal approachi. Using two or more different classes of drugs simultaneously to interrupt the

pain pathway at various pointsc. Pharmacologic Management

i. Non-Opioid analgesics1. Non-steroidal anti-inflammatory drugs (NSAIDs)

a. Administer at their lowest effective analgesic dose in the EDand upon discharge

b. Give for the shortest appropriate treatment coursec. Use with caution in patients at risk for renal insufficiency,

heart failure, gastrointestinal adverse effectsd. Consider topical preparations if systemic use is

contraindicated2. Acetaminophen (APAP)

a. Oral and rectal forms of acetaminophen (APAP) either aloneor in combination provide similar efficacy to IV APAP but withslower onset of action

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b. Use oral or rectal dosage forms unless contraindicated 3. Regional Anesthesia

a. Consider regional and local nerve blocks alone or in combination with other modalities

4. Lidocaine a. Limited data suggests may alleviate specific painful conditions

(renal colic, herpetic/post-herpetic neuralgia) 5. Ketamine

a. Low-dose ketamine administered alone or as part of a multimodal analgesic approach may be considered in the ED

III. Table 1. Commonly used Non-Opioid Analgesics13-14

Medication Initial Dosing Limitations

Acetaminophen 650 mg – 1000 mg PO/rectal suppository/IV

Limited efficacy as monotherapy in moderate to severe pain

NSAIDs Ibuprofen 400-800 mg PO Naproxen 250-500 mg PO Ketorolac 15-60 mg IV/IM

Limited efficacy as monotherapy in moderate to severe pain, potentially serious adverse effects, requires caution in multiple disease states

Muscle relaxants Cyclobenzaprine 5-10 mg PO

Primarily used for musculoskeletal pain only

Anticonvulsants Gabapentin 100-300 mg PO Pregabalin 75-150 mg PO

Primarily used for neuropathic pain only

Antidepressants Amitriptyline 5-10 mg PO Primarily used for neuropathic pain only IV: intravenous, PO: by mouth, IM: intramuscular

i. Opioid Analgesics

1. Emergency medicine clinicians are uniquely positioned to combat the opioid epidemic by:

a. Thoughtful prescribing of parenteral and oral opioids in the ED and upon discharge

b. Engagement with opioid addicted patients in the ED 2. Parenteral opioids when used in titratable fashion are effective, safe

and easily reversible analgesics that quickly relieve pain 3. Consider opioids when benefit is greater than risks 4. Oral opioid administration is effective for most patients in the ED and

immediate release morphine sulfate is associated with less euphoria

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Table 2. Commonly used opioid analgesics12,15-16

Medication Initial Dosing Side effects

Morphine 0.1 mg/kg IV Constipation*

Sedation*

Respiratory depression*

Hypotension*

Opioid-induced hyperalgesia*

Histamine-release

Hydromorphone 0.015 mg/kg IV Seizures (dose-dependent)

Fentanyl 1-1.5 mcg/kg IV Serotonin syndrome

Tramadol 50 mg PO Serotonin syndrome

Increase seizure risk

Hydrocodone/APAP 5/325 mg- 10/325 mg PO Increase liver toxicity *Indicated side effect common amongst all opioids; IV: intravenous, PO: by mouth

IV. Limitations to Opioids

a. Adverse effects i. Listed in table 2

b. Opioid-induced hyperalgesia17 i. Defined as state of nociceptive sensitization caused by exposure to opioids

ii. Characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could become more sensitive to certain painful stimuli

iii. Treatment options include: 1. Discontinuing the offending opioid, adding a COX-2 inhibitor may be

beneficial 2. Antagonizing the NMDA receptor with ketamine may also be a

reasonable strategy V. Opioid Crisis

a. History and epidemiology18-21 i. In the late 1990s, pharmaceutical companies reassured the medical

community that patients would not become addicted to prescription opioid pain relievers

ii. Healthcare providers began to prescribe opioids at greater rates iii. This lead to widespread diversion and the misuse of opioids iv. In 2017, more than 47,000 Americans died due to an opioid overdose v. An estimated 1.7 million people suffered from a substance use disorder

related to prescription opioid pain relievers in 2017 vi. On average, 130 Americans die every day from an opioid overdose

b. Economic Burden22 i. CDC estimates that the total economic burden of prescription opioid misuse

alone in the US is $78.5 billion a year c. What do we know about the opioid crisis?

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i. Roughly 21 to 29% of patients prescribed opioids for chronic pain misuse them

ii. Between 8 and 12% of patients develop an opioid use disorder d. Role of ED in opioid crisis23-24

i. ED may foster a role in the development of opioid addiction and dependence ii. ED sees many patients for various pain-related problems

iii. Many patients frequently receive their first opioid treatment in the ED iv. Patients with moderate to severe pain are often sent home with an opioid

prescription if successfully treated with an opioid in the ED

Ketamine I. Background25-26

a. History of ketamine i. Developed in 1960s as a PCP derivative

ii. Classified as a schedule III controlled substance in 1999 b. Negative stigma

i. “Club drug” ii. Date rape drug

iii. Hallucinogenic effects II. Indications25-26

a. Approved in 1970 by the Food and Drug Administration (FDA) i. Induction and maintenance of anesthesia

b. Potential indications i. Depression

ii. Rapid sequence intubation iii. Asthma iv. Agitation v. Alcohol withdrawal

vi. Acute pain vii. Chronic pain

viii. Status epilepticus III. Dosing and dosage forms27

a. Routes include IV, Sub-Q, IM, oral, rectal, topical, intranasal, and sublingual

Table 3. Ketamine Dosing Ranges

Dose Effect

0.1-0.3 mg/kg Analgesia

0.2-0.5 mg/kg Recreational

0.4-0.8 mg/kg Partially dissociated

>0.8 mg/kg Fully dissociated

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IV. Mechanism of Action25,28

a. Non-competitive antagonist of CNS N-methyl-D-aspartate (NMDA) receptorb. Agonist at alpha and beta adrenergic receptorc. Antagonist at muscarinic receptord. Blocks reuptake of catecholaminese. Agonist at opioid receptors

V. Pharmacologic effectsa. Central nervous system (CNS)

i. Sedation1. Produces a catatonic state

ii. Analgesia1. Inhibits binding of excitatory amino acids (glutamate and aspartate)

to the NMDA receptor in the CNS, blocking the transmission of painfulstimuli

2. NMDA antagonism produces analgesia and limits the development ofopioid tolerance and hyperalgesia

iii. Cardiovascular1. Elevates circulating epinephrine and norepinephrine leading to

increased heart rate, blood pressure, cardiac output, and vascularresistance

iv. Respiratory1. No respiratory depressant effects when given in low doses

VI. Pharmacokinetics25

Table 4. Ketamine Pharmacokinetics

Onset of Action IV: 30-60 seconds

Duration of Action IV: 10-15 minutes

Distribution Lipid soluble able to rapidly cross blood brain barrier

Metabolism Liver via N-dealkylation Major metabolite is norketamine

Elimination Kidneys (urine 91%)

VII. Adverse Effects25

a. Dizzinessb. Psychomimetic effects such as feelings of unrealityc. Nausea and vomitingd. Tachycardiae. Hypertensionf. Emergence reactions

VIII. Emergence reactions25,29

a. Visual and auditory disturbances such as feelings of unreality, hallucinations,anxiety, paranoia

b. May range from mild to extreme discomfortc. Occurs when “emerging” from dissociative state

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d. No emergence reaction with subdissociative doses because the patient wasn’t everin a true dissociative state

e. Rescue medicationsi. Benzodiazepines

f. Anticipation of emergence reactions are the number-one reason physicians fear theuse of LDK in the emergency department

IX. Contraindications25

a. Absolutei. Allergy to ketamine

ii. Acute psychosis1. Ketamine may exacerbate psychosis

iii. Age <3 months1. Reported cases of airway obstruction, laryngospasm and apnea;

represents infant-specific differences in airway anatomyb. Relative

i. Pregnancy ketamine is a C drug (as are all opioids)1. Recommend not to use in first trimester but can consider use in

second and third trimester after having discussion of risk/benefit withpatient

ii. Altered mental statusiii. Acute thyrotoxicosisiv. Elevated intraocular pressurev. Cardiovascular disease, specifically acute decompensated heart failure and

acute coronary syndromeX. Monitoring

a. Prior to administration, baseline vital signs (VS) should be obtained and documentedb. During and after administration, frequent VS monitoring and documentation should

be conducted

Literature Review

I. Clinical Question: Is low-dose ketamine SAFE and EFFECTIVE for use in acutepain management in the emergency department?

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Table 3. Motov S, et al. Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial. Ann Emerg Med. 2015;66:222-229.

Objective

Assess and compare the analgesic efficacy and safety of LDK with morphine in ED patients

Methods

Prospective, randomized, double-blind controlled trial

Patient Population

Inclusion

Age 18 to 55 years old

Acute abdominal, flank, back ormusculoskeletal pain

Numeric rating scale (NRS) score of equal to orgreater than 5 of 10

Deemed by the treating ER physician torequire opioid analgesia

Exclusion

Pregnancy/breast-feeding

Altered mental status

Allergy to morphine or ketamine

Weight 46 kg or >115 kg

Unstable vital signs

Medical history of acute head or eye injury,seizure, intracranial hypertension, chronicpain, renal or hepatic insufficiency, alcoholor drug abuse, psychiatric illness or recentopioid use (4 hours before)

Intervention

Ketamine 0.3 mg/kg IV push over 3-5 minutes

Morphine 0.1 mg/kg IV push over 3-5 minutes

If patients reported a pain numeric scale score of 5 or greater and requested additional painrelief, fentanyl 1 mcg/kg was administered as a rescue analgesic

Outcomes

Primary Outcomes:

Comparative reduction of numeric rating scalepain scores between recipients of ketamineand morphine at 30 minutes

Secondary Outcomes:

Need for rescue analgesia at either 30 or 60minutes

Changes to vital signs

Adverse effects

Statistics

Frequency distributions, paired t test and independent-sample t test

Baseline Characteristics

N= 90 (ketamine n=45, morphine n=45)

Baseline characteristics similar (i.e. age, gender, blood pressure, source of pain)

At the start, baseline pain scores for ketamine and morphine were 8.6 and 8.5

Results

Primary Outcome

The primary change in mean pain scores was not significantly different in the ketamine andmorphine groups

Mean difference in pain score of 4.1 versus 3.9 at 30 minutesSecondary OutcomesAdverse Effects: Ketamine vs Morphine

Dizziness:o 15 minutes: 53% vs 31%o 30 minutes: 8% vs 6%

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Disorientation:o 15 minutes: 11% vs 0%o 30 minutes: 1% vs 0%

Mood Changes:o 15 minutes: 11% vs 0%o 30 minutes: 1% vs 0%

Nausea:o 15 minutes: 18% vs 11%o 30 minutes: 6% vs 9%

The ketamine group experienced statistically more significant adverse effects in the first 15minutes

Most side effects dissipated by 30 minutes

No changes in vital signs that were clinically concerning or required interventionFentanyl Rescue Incidence:Ketamine vs Morphine

15 minutes: 0% vs 0%

30 minutes: 4% vs 1%

60 minutes: 4% vs 6%

No statistically significant difference in the use of rescue fentanyl analgesia at 30 or 60 minutes

Conclusion

Ketamine administered at 0.3 mg/kg provides analgesic effectiveness and apparent safety comparable to that of IV morphine for short-term treatment of acute pain in the ED.

Critique

Strengths

Randomized, double-blind trial

Limitations

Single center

Small patient size

Chronic pain patients excluded from study

Potential for unblinding due to nystagmusreaction

Table 4. Bowers K, et al. Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial. Society from Academic Emergency Medicine. 2017;24(6):676-685.

Objective

Assess and compare the analgesic efficacy and safety of low-dose ketamine compared to placebo, as an adjunctive treatment to opioids

Methods

Prospective, randomized, double-blind controlled trial at a single academic emergency department

Patient Population

Inclusion

Age 18 to 70 years old

Numeric rating scale (NRS) score of equal to orgreater than 6 of 10

Deemed by the treating ER physician torequire opioid analgesia

Exclusion

Respiratory, hemodynamic, or neurologiccompromise

History of chronic ventilation or dialysis orwith previously diagnosed cirrhosis orhepatitis by history

Active psychosis

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Clinical intoxication

Known sensitivity to study drug

Inability to understand the NRS-11 painmanagement scale

Presentation with headache or chest pain

Pregnancy

Lack of decision-making capacity

History of narcotic abuse

Intervention

Patients received initial provider-determined treatment

Patients reassessed after 15 minutes and if, after initial dose patient reported pain > 6/10 thenrandomized to:

o Ketamine 0.1 mg/kg IV push over 1 minute ORo Equivalent volume of normal saline (placebo)

Repeat doses of pain medication were given as 0.05 mg/kg morphine or equivalent dose of opioid analgesic when requested by the participant

Outcomes

Primary

Level of pain control

Satisfaction with pain control

Secondary

Total amount of opioids given

Adverse effects

Statistics

Wilson rank sum tests, chi-squared tests, and Fischer’s exact test, t tests

Baseline Characteristics

N=116

Mean age: ~42 years

Female: 44%

Prior opioid use: 25.9%

Chief complaint: Mostly abdominal pain 37.9%

Results

Primary Outcome: Patients receiving ketamine reported lower pain scores over 120 minutes than patients receiving placebo

P=0.015Patient satisfaction (mean + SD)

Ketamine: mean + SD = 2.66 + 0.67

Placebo: mean + SD = 2.52 + 0.50

Not a statistically significant differenceSecondary Outcome:Total opioid dose

Ketamine: mean + SD = 9.95 + 4.83 mg

Placebo: mean + SD = 12.81 + 6.81 mg

Statistically significant difference in total opioid dose between the two treatments (p=0.02)

Fewer repeat doses of analgesia in the ketamine group

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Adverse Effects: Ketamine versus Placebo

Nausea: 4 (7.6%) vs 3 (4.8%)

Light-headedness or dizziness: 16 (30.2%) vs 5 (7.9%)

Dry mouth: 0 vs 2 (3.2%)

Disorientation: 0 vs 1 (1.6%)

Euphoria: 1 (1.9%) vs 1 (1.6%)

Nystagmus: 2 (3.78%) vs 0

12 patients in placebo group and 27 in ketamine group reported side effects

No patient had side effects lasting longer than 6 minutes

Conclusion

Ketamine, as an adjunct to opioid therapy, was more effective at reducing pain over 120 minutes and resulted in a lower total opioid dose as well as fewer repeat doses of analgesia.

Critique

Strengths

Randomized, double-blind

Assess side effects immediately after medicationadministration

Included patients with chronic pain

Limitations

Single center

Small patient size

Some patients received proceduralanalgesia and/or non-opioid rescuemedications

Initial provider dose was not consistent

Table 5. Sin et al. The use of ketamine for acute treatment of pain: A randomized, double-blind, placebo-controlled trial. J Emerg Med. 2017;52(5): 601-608.

Objective

Evaluate LDK as an adjunct for acute pain in the ED

Methods

Single center, prospective, randomized, double-blind controlled, placebo controlled trial

Patient Population

Inclusion

Age 18 or older

English speaking

Chief complaint of acute pain with a numericrating scale (NRS) score of equal to or greaterthan 3 of 10

Acute pain was defined as onset of less thanor equal to 15 days

Exclusion

Hemodynamic instability

Altered mental status

Weight >166 kg

Pregnancy/breastfeeding

Allergy to study drugs

Opioid use <=4 hours of presentation to ED

Medical history of schizophrenia,depression, or substance abuse

Traumatic head injury, headache, migraine,or increased intracranial or intraocularpressure

Intervention

All patients received morphine 0.1 mg/kg IV push (max 10 mg) then randomized to:o Ketamine 0.3 mg/kg in 50 mL normal saline IVPB over 15 minutes oro Normal saline 50 mL infused over 15 minutes (placebo)

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Outcomes

Primary Outcomes:

NRS score after 15 minutes

Secondary Outcomes:

Incidence of adverse effects

Mean consumption of rescue analgesia

Patient’s length of stay in the ED

Patient satisfaction

Statistics

Kolmogorov Smirnov tests, Mann-Whitney U tests, t tests

Baseline Characteristics

N=60 (30 in ketamine group and 30 in placebo group)

Average age ~48 years

Most patients presented with abdominal or musculoskeletal pain

Mean baseline numeric rating scale >8 in both groups

Results

Study Outcomes Primary Outcome

Pain scores were significantly lower in the ketamine group than the placebo group at 15 minutesand 30 minutes after administration

Median pain score at 15 minutes: ketamine 3.5 vs placebo 6.0

P= 0.018Secondary Outcomes

No significant difference in the amount of rescue opioids used between the groups

Statistically significant difference in patient satisfaction, favoring ketamine (8.57 vs 6.05, p=0.01)

No difference in length of stay in EDAdverse Events

No statistically significant difference in adverse effects between groups

Dizziness (53%) and disorientation (29%) were frequently reported immediately after ketamineinjection

Conclusion

When used as an adjunct, LDK administered at 0.3 mg/kg over 15 minutes resulted in safe and effective analgesia for at least 30 minutes in patients who presented with acute pain in the ED

Critique

Strengths

Randomized, double-blind

Used short infusion of ketamine instead of IVpush

Limitations

Single center

Small patient size

Clinical diagnosis not evenly distributed

Table 6. Motov S, et al. A prospective randomized, double-dummy trial comparing IV push low dose ketamine to short infusion of low dose ketamine for treatment of pain in the ED. American Journal of Emergency Medicine. 2017. 1095-1100.

Objective

Compare adverse effects and analgesic efficacy of low-dose ketamine for acute pain in the ED administered either by single intravenous push (IVP) or short infusion (SI)

Methods

Prospective, randomized, double-blind, double-dummy trial

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Patient Population

Inclusion

Age 18 to 65 years old

Primary complaint of acute abdominal flank,or musculoskeletal pain with initial pain score> 5 on the numeric pain rating scale (NRS)

Awake, alert and oriented to person, placeand time

Exclusion

Pregnancy/breast-feeding

Altered mental status

Allergy to ketamine

Weight <46 kg or >115 kg

Unstable vital signs

Medical history or acute head or eye injury,seizure, intracranial HTN, renal or hepaticinsufficiency, alcohol or drug abuse,psychiatric illness or recent (4 hours before)analgesic use

Intervention

Ketamine 0.3 mg/kg via IV push (over 5 minutes)

Ketamine 0.3 mg/kg mixed in 100 mL NS via short infusion (over 15 minutes)

If patients still desired pain medication, they were offered IV morphine 0.1 mg/kg as a rescueanalgesic

Outcomes

Primary Outcomes:

Overall rates of specific side effects andspecific severity levels of the side effects ratedfrom 0-4 on the Side Effects Rating Scale forDissociative Anesthetics (SERSDA)

Severity of agitation and/or sedation rated byRASS score

These were measured at 15, 30, 60, 90, and120 minutes post administration

Secondary Outcomes:

Analgesic efficacy (NRS score)

Changes in vital signs

Need for rescue analgesia

Statistics

Student t-tests, chi square tests

Baseline Characteristics

N= 48 (IVP: 24, SI 24)

Baseline characteristics similar (i.e. age, gender, chief complaint, etc.)

Mean age: early 40s

Mean baseline pain score: >8 in both groups

Results

Primary Outcome: Side effects- Feeling of Unreality on SERSDA

IVP: 91.7%

IV infusion 54.2%

P=0.008

NNH: 3

SERSDA= side effects rating scale for dissociative anestheticsRates of Sedation (RASS)

RAAS scale at 5 minutes was greater in the IVP group

Median RAAS – 2.0 versus 0.0

P=0.01

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Secondary Outcomes

No difference in reduction in pain scores, change in vital signs or need for rescue analgesia

Conclusion

Low-dose ketamine given as a short infusion is associated with significantly lower rates of feeling of unreality and sedation with no difference in analgesic efficacy in comparison to intravenous push.

Critique

Strengths

Randomized, double-blind

Limitations

Single center

Small patient size

Conclusion I. Overall

a. Ketamine is safei. No major adverse effects occurred in the literature review studies

ii. Higher rate of minor side effects, but usually short lived and tolerableb. Ketamine is effective

i. LDK alone is comparable to morphine 0.1 mg/kgii. LDK as an adjunct to opioids improved pain control versus IV opioids alone

II. Treatment Recommendationsa. Multimodal approach to pain management is recommended

i. Use combination of non-pharmacologic treatments, non-opioids and opioidsif necessary

b. When should ketamine be considered?i. NRS score >6

ii. Patients who use opioids chronicallyiii. Opioids are contraindicatediv. Opioids not tolerated by patientv. Opioids are ineffective

vi. Opioids are not desired by the patientvii. Opioids are not desired by the physician

c. How should ketamine be given?i. Ketamine 0.3 mg/kg in 100 mL NS over 15 minutes

Figure 2. Pain Ladder

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Fig. 3 Ketamine Algorithm

Fig. 4 Summary of Pain Management

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